Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5-9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. Graphical abstract.The tissue factor/coagulation factor VIIa (TF/FVIIa) complex induces transactivation of the IGF-1 receptor (IGF-1R) in a number of different cell types. The mechanism is largely unknown. The transactivation leads to protection from apoptosis and nuclear translocation of the IGF-1R. The aim of this study was to clarify the signaling pathway between TF and IGF-1R after FVIIa treatment with PC3 and DU145 prostate or MDA-MB-231 breast cancer cells as model systems. Protein interactions, levels, and phosphorylations were assessed by proximity ligation assay or flow cytometry in intact cells and by western blot on cell lysates. The transactivation of the IGF-1R was found dependent on TF/FVIIa-induced activation of β1-integrins. A series of experiments led to the conclusion that the caveolae protein caveolin-1 prevented IGF-1R activation in resting cells via its scaffolding domain. TF/FVIIa/β1-integrins terminated this inhibition by activation of Src family kinases and subsequent phosphorylation of caveolin-1 on tyrosine 14. This phosphorylation was not seen after treatment with PAR1 or PAR2 agonists. Consequently, the protective effect of FVIIa against apoptosis induced by the death receptor agonist TRAIL and the de novo synthesis of cyclin D1 induced by nuclear IGF-1R accumulation were both significantly reduced by down-regulation of β1-integrins or overexpression of the caveolin-1 scaffolding domain. In conclusion, we present a plausible mechanism for the interplay between TF and IGF-1R involving FVIIa, β1-integrins, Src family proteins, and caveolin-1. Our results increase the knowledge of diseases associated with TF and IGF-1R overexpression in general but specifically of TF-mediated signaling with focus on cell survival.Optimal management of intracranial pressure (ICP) among aneurysmal subarachnoid hemorrhage (aSAH) patients requiring external ventricular drainage (EVD) is controversial. To analyze predictors of delayed cerebral ischemia (DCI)-related cerebral infarction after aSAH and the influence of ICP values on DCI, we prospectively collected consecutive patients with aSAH receiving coiling and requiring EVD. Predictors of DCI-related cerebral infarction (new CT hypodensities developed within the first 3 weeks not related to other causes) were studied. Vasospasm and brain hypoperfusion were studied with CT angiography and CT perfusion (RAPID-software). Among 50 aSAH patients requiring EVD, 21 (42%) developed DCI-related cerebral infarction, while 27 (54%) presented vasospasm. Mean ICP ranged between 2 and 19 mmHg. On the multivariate analysis, the mean ICP (OR = 2, 95%CI = 1.01-3.9, p = 0.042) and the mean hypoperfusion volume on Tmax delay &gt; 6 (OR = 1.2, 95%CI = 1.01-1.3, p = 0.025) were independent predictors of DCI. To predict DCI-related cerebral infarction, Tmax delay &gt; 6 s presented the highest AUC (0.956, SE = 0.025), with a cutoff value of 18 ml showing sensitivity, specificity, PPV, NPV, and accuracy of 90.5% (95%CI = 69-98.8%), 86.2% (95%CI = 68.4-96%), 82.6% (95%CI = 65.4-92%), 92.5% (95%CI = 77-98%), and 88% (95%CI = 75-95%), respectively. The AUC of the mean ICP was 0.825 (SE = 0.057), and the best cutoff value was 6.7 mmHg providing sensitivity, specificity, PPV, NPV, and accuracy of 71.4% (95%CI = 48-89%), 62% (95%CI = 42-79%), 58% (95%CI = 44-70%), 75% (95%CI = 59-86%), and 66% (95%CI = 51-79%) for the prediction of DCI-related cerebral infarction, respectively. Among aSAH patients receiving coiling and EVD, lower ICP ( 6 s presents a high sensibility and specificity in prediction of DCI-related cerebral infarction.Idiopathic intracranial hypertension (IIH) is a rare disease with an incidence rate of 0.5-2.0/100,000/year. Characteristic symptoms are headache and several degrees of visual impairment. Psychiatric symptoms in association with IIH are usually poorly described and underestimated. In this study, we evaluated IIH subjects to determine the association with psychiatric symptoms. We evaluated thirty consecutive patients with IIH submitted to neurosurgery from January 2017 to January 2020 in two Brazilian tertiary hospitals. https://www.selleckchem.com/products/GDC-0980-RG7422.html They underwent clinical evaluation, obtaining medical history, comorbidities, body mass index (BMI-kg/m2), and applying Neuropsychiatric Inventory Questionnaire (NPI-Q). There were 28 females and 2 males. Ages ranged from 18 to 66 years old, with mean age of 37.97 ± 12.78. Twenty-five (83%) presented comorbidities, being obese and having arterial hypertension the most frequent. Body mass index ranged from 25 to 35 kg/m2 and mean value was 31 ± 3.42. After application of Neuropsychiatric Interview, 26 of 30 presented psychiatric symptoms (86%). Depression-anxiety syndromes were reported in 25 patients (83%). Nighttime disturbances were reported by 14 subjects (46%). Appetite and eating disorders were described by 23 (76%). Psychiatric symptoms in association with IIH are usually poorly described and underestimated. In our sample, twenty-six out of 30 (86%) reported psychiatric symptoms. We highlight the high prevalence of psychiatric symptoms among IIH patients and the need of managing these patients with a multidisciplinary team, including psychiatrists.